A core facility will be established for the chemical synthesis of short double-helical DNA molecules of variable sequence. Some of these DNA duplexes will contain either 5-methyl cytosine, a ribonucleotide, or a stable isotope at defined positions in the sequence. These products will be studied by a variety of physical methods including high-resolution NMR, solid-state NMR, saturation-transfer EPR, dynamic laser light scattering, fluorescence polarisation anisotropy decay and ODMR in order to investigate the fundamental structural and dynamic principles underlying the sequence-specific recognition of DNA by proteins. In addition short synthetic DNAs will be used for site-directed mutagenesis studies of genetic regulation and in studies on the synthesis of novel sequence-specific intercalative drugs. We propose to construct, to our own design sepcifications, an extremely sophisticated and highly flexible superconducting spectrometer which will be capable of carrying out all the NMR experiments described in this program.